Molecular mechanisms whereby skeletal muscle adaptation mediate the health benefits of exercise training.
The overall goal of our work is directed at gaining a better understanding of cellular signaling pathways and mechanisms responsible for the adaptive responses of skeletal muscle to normal physiologic stimuli – such as occurs in exercise training – and to maladaptive responses to pathophysiologic stimuli – such as occurs in congestive heart failure, skeletal muscle atrophy associated with chronic spaceflight and aging. We are using human studies, animal models and in vitro models of exercise to address these scientific questions. One of our underlying assumptions is that much of the signaling in response to exercise occurs as mechanotransduction from the external environment to the nucleus, resulting in altered gene expression for metabolic, structural and signaling proteins.
Our in vitro models are designed to explore whether mechanical deformation of skeletal muscle cells (mechano-transduction) are responsible for some of the skeletal muscle responses to changes in contractile activity. For example, we use a unilateral stretch device of our own design to explore changes induced by stretch and modifications of our design of a rotating cell culture system to explore changes induced by simulated microgravity. Students in our laboratory learn the essentials of molecular biology techniques in the context of addressing mechanistic questions of interest to the laboratory. Students are also instructed in scientific writing and presentation and learn how to ask meaningful scientific questions and pose hypotheses in order to develop and write scientific applications.
Another focus of our work is physiologic examination of exercise effects in human subjects in clinical trials of exercise training in normal individuals, in individuals at risk of disease (such as pre-diabetes), and in individuals with disease (such as coronary heart disease and congestive heart failure). We explore skeletal muscle adaptation at the protein and gene expression levels. A final area is exploration of genetic determinates of disease risk in human subjects. We conduct studies of early onset cardiovascular disease (GENECARD), congestive heart failure (HF-ACTION) , peripheral artery disease (AMNESTI) and metabolic syndrome (STRRIDE. We are involved in exploring analytic models of predicting disease risk and cardiometabolic adaptations to exercise training using established and new statistical methodology.